B cell tetherin: a flow‐cytometric cell‐specific assay for response to Type‐I interferon predicts clinical features and flares in SLE

Objective: Type I interferon (IFN-I) responses are broadly associated with autoimmune disease including SLE. Given the cardinal role of autoantibodies in SLE, we investigated whether a B cell-specific IFN assay might correlate with SLE activity. Methods: B cells and PBMCs were stimulated with IFN-I and IFN-II. Gene expression was scrutinized for pathway-related membrane protein expression. A flow-cytometric assay for tetherin (CD317), an IFN-induced protein ubiquitously expressed on leucocytes, was validated in vitro then clinically against SLE diagnosis, plasmablast expansion, and BILAG-2004 score in a discovery cohort (156 SLE; 30 RA; 22 healthy controls). A second longitudinal validation cohort of 80 patients was also evaluated for SLE flare prediction. Results: In vitro, a close cell-specific and dose-responsive relationship between IFN-I responsive genes and cell surface tetherin in all immune subsets existed. Tetherin expression on multiple cell subsets was selectively responsive to stimulation with IFN-I compared to IFN-II and -III. In patient samples from the discovery cohort memory B-cell tetherin was best associated with diagnosis (SLE/HC: effect size=0.11, p=0.003; SLE/RA: effect size=0.17, p